The purpose of this study was to develop formulation and systematically evaluate in vitro performances of mucoadhesive patches of Esomeprazole magnesium trihydrate using HPMC K4M, HPMC (15cps), and HPMC (5cps) for avoiding gastric degradation and prolong the release up to 8 h. The films were smooth and elegant in appearance, uniform in thickness, weight, drug content and good folding endurance. Drug and polymer incompatibility was not shown in FTIR study. In-vitro release studies were reveal that all films exhibited sustained release in range of 87.31 to 98.04% for a period of 8 h. Ex-vivo permeation studies of Esomeprazole magnesium trihydrate were shown in the range of 84.35 to 91.33%.The best mucoadhesive performance and prolonged release was exhibited by formulation F2. Formulation F2 was shown 91.45% drug release after 8 h and 28.4 gm mucoadhesive force. It was followed zero order drug release pattern and non-fickian release behavior. Therefore, buccal patches containing HPMC K4M (3%) was shown satisfactorily results for alternative route of administration of Esomeprazole magnesium trihydrate for avoiding gastric degradation and sustain release.